The visual system has been relatively neglected in recent MS research and often it is not examined in autopsied patients. We propose to study demyelination of the optic nerve clinically and experimentally. We will determine the leukocyte antigens HLA and Ia-like antigens by similar test on purified peripheral blood B-lymphocytes in Caucasian ON patients since the histocompatibility immune system may be linked to the genetic control of susceptibility to demyelinating disease. We hope to develop a test diagnostic for demyelination through studies of cellular and humoral immunity. The demyelinating activity of spinal fluid, serum or cells will be examined using two in vivo model systems of CNS demyelination: the rabbit eye chamber mode and the optic nerves of Xenopus tadpoles. Morphological studies of experimental demyelination of intraocular myelin will be performed using a new technique, whole mount preparations of the rabbit retina to show the myelin sheaths of epiretinal optic nerve fibers. A technique will be developed to isolate individual CNS fibers for measurement. Subsequent studies may permit pathophysilogical correlation of the latency of the visual evoked response with the severity of demyelination in the anterior visual system.